Breast cancer worldwide affects nearly one million women per year and although current treatments do help many patients, more than 350,000 die from the disease. In Malaysia, breast cancer is the most common cancer where the statistic shows that 18.0% of the total cancer case reported is from breast cancer. It is documented that 11,952 new breast cancer cases were reported to the National Cancer Registry within year 2003-2005, which comprised 31.3% of all cancers in women.
The established risk factors for breast cancer include a family history of breast cancer, early menarche, late age at first childbirth, late age at menopause and history of benign breast disease. With the exception of the genetic predisposition to the disease the rest of the risk factors point to the life time exposure of women to estrogen. Estrogen does not cause the disease but is involved in the progression and development of breast cancer. Anti-estrogens are therefore used as therapy in the control of breast cancer progression.
Scientific investigations have been undertaken to associate possible functional properties, antioxidant or otherwise in the diet, which could be efficient in preventing diseases like cancer. One such antioxidant is vitamin E. The tocotrienol (or T3) group together with tocopherols compose the vitamin E family. Both have four isomers, which are α-, β-, γ-, δ-tocopherols and α-, β-, γ-, δ-Tocotrienols (Machlin et al., 1991).
The major structural difference of tocotrienol from tocopherol is through its unsaturated side chain that has three double bonds in its farnesyl isoprenoid tail. Tocotrienols also display a variety of functions that are clearly distinct from that of α-tocopherols (Sen et al., 2006) Tocopherols are abundant in common vegetables and nuts, while tocotrienols can be found in rice bran, wheat germ and most abundantly in the fruit of palm (Sundram, et al., 2002; Sookwong, et al., 2007). Crude palm oil extracted from the fruits of oil palm (Elaeis guineensis) particularly contains a larger concentration of tocotrienols (up to 800 mg kg−1) than all other natural sources (Theriault et al., 1999). The tocotrienol-rich fractions (TRF) composed of 32% α-tocopherol and 68% tocotrienols can be obtained from palm oil after esterification and following distillation, crystallization and chromatography (Sundram et al., 1992).
Tocotrienol isomers of vitamin E in palm oil have been reported to contain biological and physiological properties which include potential blood cholesterol lowering and cardioprotective effects, efficient antioxidant activity in biological systems, and possible anticancer and neuroprotective effects (Sen et al., 2006).
Previous studies showed that tocotrienols are the components of vitamin E responsible for growth inhibition in human breast cells in vitro as well as in vivo (Nesaretnam et al., 1998). The inhibitory effects on cancer cell growth was found to be different in the four isomers of tocotrienols with studies reported that γ- and δ-tocotrienols have pronounced inhibitory effect compared to α- and β-tocotrienol (Yu et al., 1999). TRF and δ- and γ-tocotrienol are shown to inhibit the proliferation of PC-3, a prostate cancer cell whereas α-tocopherol showed no significant effects (Nesaretnam et al., 2008). Various findings have demonstrated the superiority of tocotrienols over tocopherols in terms of their anti-cancer property. Tocotrienols, but not tocopherols, inhibited the growth of normal mouse mammary epithelial cells, ZR-75-1, a responsive human breast cancer line and MDA-MD-435 oestrogen-receptor-negative human breast cancer cells (McIntyre et al., 2000; Nesaretnam et al., 2000; Nesaretnam et al., 1995). Noguchi and colleagues (2003) reported that α-tocotrienol suppresses the expression of vascular cell adhesion molecule-1 (VCAM-1) and the adhesion of THP-1 monocytic cells to human umbilical vein endothelial cells (HUVECs). In fact, the efficacy shown by α-tocotrienol was 10-fold higher than that of α-tocopherol. In addition, α-tocotrienol also exhibits neuroprotective activities through its protection against glutamate- and stroke-induced neurodegeneration, a property not seen in α-tocopherol (Khanna et al., 2005).
In recent years, the medicinal properties of turmeric and its bioactive compound curcumin have increasingly been recognized. Curcumin, a bioactive constituent derived from the rhizomes of Curcuma longa is one of the major yellow pigments found in turmeric and has over many years of history in traditional medicinal uses. There are many evidences for its cytotoxic, antiproliferative, and/or proapoptotic activity toward neoplastic cells in vitro, and suppression of tumorigenesis in rodent models (Sharma et al., 2005; Duvoiz et al., 2005; Aggarwal et al., 2005). These findings further give ways for curcumin's translation into therapeutic modalities to combat cancer. Previous study has shown curcumin potentiates the growth inhibitory effect of celecoxib by shifting the dose-response curve to the left. The synergistic growth inhibitory effect was mediated through a mechanism that probably involves inhibition of the COX-2 pathway and may involve other non COX-2 pathways (Lev-Ari et al., 2005). Extracellularly, curcumin acts as a strong antioxidant (Subramaniam et al., 1994; Mukundan et al., 1993) an anti-inflammatory agent and reduces free radical production (Huang et al., 1991). Curcumin is a small, lipophilic molecule that can pass through the cell membranes and exert intracellular effects as well. Curcumin's most observed property is its pronounced anti-proliferative action, described in several cell types, including colon (Ramsewak et al., 2000) and microglial (Lim et al., 2001) cells as well as its ability to induce apoptosis in cancer cells (Ruby et al., 1995). Curcumin also known to disrupts the conformation of the p53 protein required for its serine phosphorylation, its binding to DNA, its transactivation of p53-responsive genes and p53-mediated cell cycle arrest (Moss et al., 2004). Menon et al (1995) reported that curcumin-induced inhibition of B16F-10 melanoma lung metastasis in mice. Oral administration of curcumin at concentrations of 200 nmol/kg body weight reduced the number of lung tumor nodules by 80%. The life span of the animals treated with curcumin was increased by 143.85% (Menon et al., 1995).